title: Abrogated inflammatory response promotes neurogenesis in a murine model of Japanese encephalitis.
abstract: BACKGROUND
  Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.
  
  
  RESULTS
  Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.
  
  
  CONCLUSIONS
  This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Das
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.forename: Kanhaiya Lal
authors.initials: KL
authors.lastname: Kumawat
authors.forename: Ayan
authors.initials: A
authors.lastname: Ghoshal
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Adhya
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000187:drug effects / Q000502:physiology; D004672:Encephalitis, Japanese / Q000150:complications* / Q000473:pathology* / Q000821:virology; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D008911:Minocycline / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D012995:Solubility / Q000187:drug effects; D014771:Virion / Q000187:drug effects / Q000378:metabolism
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D008911:Minocycline